Special Issue "Diagnosis and Treatment of Primary and Secondary Lung Cancers"

A special issue of Cancers (ISSN 2072-6694). This special issue belongs to the section "Clinical Trials of Cancer".

Deadline for manuscript submissions: 20 June 2022.

Special Issue Editor

Prof. Francesco Petrella
E-Mail Website
Guest Editor
1. Department of Thoracic Surgery, IRCCS European Institute of Oncology, Milan, Italy
2. Department of Oncology and Hemato-oncology, University of Milan, Milan, Italy
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

Both primary and secondary tumors of the chest are major issues for clinicians; in fact, on the one hand, primary lung cancer is one of the most frequently diagnosed cancers and is the leading cause of cancer-related death worldwide. On the other hand, the lung is the second most common site of metastases, and pulmonary metastasectomy is the most frequent surgical resection undertaken by thoracic surgeons. Significant developments have recently been shown in clinical settings, both in terms of diagnosis and treatment: for example, the early diagnosis of lung nodules by computed tomography screening, circulating miRNA detection, minimally invasive diagnostic and therapeutic approaches such as endobronchial ultrasound, video-assisted thoracic surgery and robot-assisted thoracic surgery, immunotherapy, TKI inhibitors, and stereotactic body radiation therapy (SBRT) represent only some of the most significant and recent goals.

Moreover, other thoracic malignancies such as chest wall tumors, mediastinal tumors, and mesothelioma, although rare, represent the most advanced frontier of modern oncology.

In this Special Issue, we would like to focus on the most significant cornerstones in the diagnosis and therapy of both primary and secondary thoracic cancers.

It is our pleasure to lead such a comprehensive issue, and we look forward to receiving your valuable contributions.

Prof. Francesco Petrella
Guest Editor

Manuscript Submission Information

Manuscripts should be submitted online at www.mdpi.com by registering and logging in to this website. Once you are registered, click here to go to the submission form. Manuscripts can be submitted until the deadline. All papers will be peer-reviewed. Accepted papers will be published continuously in the journal (as soon as accepted) and will be listed together on the special issue website. Research articles, review articles as well as short communications are invited. For planned papers, a title and short abstract (about 100 words) can be sent to the Editorial Office for announcement on this website.

Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). All manuscripts are thoroughly refereed through a single-blind peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. Cancers is an international peer-reviewed open access semimonthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. The Article Processing Charge (APC) for publication in this open access journal is 2400 CHF (Swiss Francs). Submitted papers should be well formatted and use good English. Authors may use MDPI's English editing service prior to publication or during author revisions.

Keywords

  • lung cancer
  • lung metastases
  • diagnosis
  • lung resection
  • computed tomography
  • positron emission tomography
  • stereotactic body radiation therapy (SBRT)
  • immunotherapy

Published Papers (8 papers)

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Editorial

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Editorial
Diagnosis and Treatment of Primary and Secondary Lung Cancers
Cancers 2021, 13(3), 448; https://doi.org/10.3390/cancers13030448 - 25 Jan 2021
Viewed by 683
Abstract
Primary and secondary lung cancers are the most common clinical conditions that thoracic surgeons have to deal with: primary lung cancer, in fact, is one of the most frequently diagnosed cancers and is the leading cause of cancer-related death worldwide [...] Full article
(This article belongs to the Special Issue Diagnosis and Treatment of Primary and Secondary Lung Cancers)

Research

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Article
Diagnostic Value of Bronchoscopy for Peripheral Metastatic Lung Tumors
Cancers 2022, 14(2), 375; https://doi.org/10.3390/cancers14020375 - 13 Jan 2022
Viewed by 146
Abstract
Although lungs are one of the most frequent sites of metastasis for malignant tumors, little has been reported about the value of bronchoscopy for lung metastases presenting with peripheral pulmonary lesions (PPLs). This retrospective cohort study investigated the diagnostic value of bronchoscopy for [...] Read more.
Although lungs are one of the most frequent sites of metastasis for malignant tumors, little has been reported about the value of bronchoscopy for lung metastases presenting with peripheral pulmonary lesions (PPLs). This retrospective cohort study investigated the diagnostic value of bronchoscopy for peripheral metastatic lung tumors. Consecutive patients who underwent diagnostic bronchoscopy with radial endobronchial ultrasound for PPLs and were finally diagnosed with metastatic lung tumors from April 2012 to March 2019 were included. We analyzed 235 PPLs, with a median size of 18.8 mm. The overall diagnostic yield was 76.6%. In a multivariable analysis, large lesion size (>20.0 mm vs. <20.0 mm: 87.6% vs. 67.7%, p = 0.043, OR = 2.26), inner location (inner 2/3 vs. outer 1/3: 84.8% vs. 69.1%, p = 0.004, OR = 2.79), and visibility on radiography (visible vs. invisible: 83.2% vs. 56.1%, p = 0.015, OR = 3.29) significantly affected the diagnostic yield. Although a positive bronchus sign tended to have a higher yield, no significant difference was observed (81.8% vs. 70.6%, p = 0.063). Only one case of lung abscess was observed, with no serious complications. In conclusion, bronchoscopy is a valuable technique for peripheral metastatic lung tumors, with good diagnostic accuracy and safety. Full article
(This article belongs to the Special Issue Diagnosis and Treatment of Primary and Secondary Lung Cancers)
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Article
Sex-Based Clinical Outcome in Advanced NSCLC Patients Undergoing PD-1/PD-L1 Inhibitor Therapy—A Retrospective Bi-Centric Cohort Study
Cancers 2022, 14(1), 93; https://doi.org/10.3390/cancers14010093 - 24 Dec 2021
Viewed by 394
Abstract
Men with non-small cell lung cancer (NSCLC) have a more favorable response to immune-checkpoint inhibitor (ICI) monotherapy, while women especially benefit from ICI-chemotherapy (CHT) combinations. To elucidate such sex differences in clinical practice, we retrospectively analyzed two cohorts treated with either ICI monotherapy [...] Read more.
Men with non-small cell lung cancer (NSCLC) have a more favorable response to immune-checkpoint inhibitor (ICI) monotherapy, while women especially benefit from ICI-chemotherapy (CHT) combinations. To elucidate such sex differences in clinical practice, we retrospectively analyzed two cohorts treated with either ICI monotherapy (n = 228) or ICI-CHT combination treatment (n = 80) for advanced NSCLC. Kaplan–Meier analyses were used to calculate progression-free (PFS) and overall survival (OS), influencing variables were evaluated using Cox-regression analyses. No significant sex differences for PFS/OS could be detected in either cohort. Men receiving ICI monotherapy had a statistically significant independent impact on PFS by Eastern Cooperative Oncology Group performance status (ECOG) ≥2 (hazard ratio (HR) 1.90, 95% confidence interval (CI): 1.10–3.29, p = 0.021), higher C-reactive protein (CRP; HR 1.06, 95%CI: 1.00–1.11, p = 0.037) and negative programmed death-ligand 1 (PD-L1) status (HR 2.04, 95%CI: 1.32–3.15, p = 0.001), and on OS by CRP (HR 1.09, 95%CI: 1.03–1.14, p = 0.002). In men on ICI-CHT combinations, multivariate analyses (MVA) revealed squamous histology (HR 4.00, 95%CI: 1.41–11.2, p = 0.009) significant for PFS; and ECOG ≥ 2 (HR 5.58, 95%CI: 1.88–16.5, p = 0.002) and CRP (HR 1.19, 95%CI: 1.06–1.32, p = 0.002) for OS. Among women undergoing ICI monotherapy, no variable proved significant for PFS, while ECOG ≥ 2 had a significant interaction with OS (HR 1.90, 95%CI 1.04–3.46, p = 0.037). Women treated with ICI-CHT had significant MVA findings for CRP with both PFS (HR 1.09, 95%CI: 1.02–1.16, p = 0.007) and OS (HR 1.11, 95%CI: 1.03–1.19, p = 0.004). Although men and women responded similarly to both ICI mono- and ICI-CHT treatment, predictors of response differed by sex. Full article
(This article belongs to the Special Issue Diagnosis and Treatment of Primary and Secondary Lung Cancers)
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Article
Endobronchial Ultrasonography with a Guide Sheath Transbronchial Biopsy for Diagnosing Peripheral Pulmonary Lesions within or near Fibrotic Lesions in Patients with Interstitial Lung Disease
Cancers 2021, 13(22), 5751; https://doi.org/10.3390/cancers13225751 - 17 Nov 2021
Viewed by 374
Abstract
In patients with interstitial lung disease (ILD), the most frequent locations of lung cancer are within or near fibrotic lesions. However, the diagnostic yield for peripheral pulmonary lesions (PPLs) within or near fibrotic lesions using endobronchial ultrasonography with a guide sheath transbronchial biopsy [...] Read more.
In patients with interstitial lung disease (ILD), the most frequent locations of lung cancer are within or near fibrotic lesions. However, the diagnostic yield for peripheral pulmonary lesions (PPLs) within or near fibrotic lesions using endobronchial ultrasonography with a guide sheath transbronchial biopsy (EBUS-GS TBB) may be unsatisfactory compared to that for PPLs distant from fibrotic lesions because of the difficulty in reaching the lesions. Our objectives were to evaluate the yield for PPLs using EBUS-GS TBB according to the proximity of PPLs to fibrotic lesions and to determine factors affecting the yield for PPLs. We retrospectively investigated 323 consecutive lesions using EBUS-GS TBB between 1 November 2014 and 31 December 2016. We identified PPLs with ILD in such lesions. PPLs with ILD were divided into PPLs within or near fibrotic lesions which met the criterion of PPLs, and of fibrotic lesions overlapping each other (PPLs-FL) and those distant from fibrotic lesions, which met the criterion of PPLs and the area of fibrotic lesion not overlapping each other (PPLs-NFL). Of the 323 lesions, 55 were included (31 PPLs-FL and 24 PPLs-NFL). The diagnostic yield for PPLs-FL was significantly lower than for PPLs-NFL (45.2% vs. 83.3%, p = 0.004). Multivariate analysis revealed that PPLs-NFL (odds ratio (OR) = 7.509) and a probe position within the lesion (OR = 4.172) were significant factors affecting diagnostic yield. Lesion’s positional relation to fibrotic lesions and the probe position were important factors affecting the successful diagnosis via EBUS-GS TBB in these patients. Full article
(This article belongs to the Special Issue Diagnosis and Treatment of Primary and Secondary Lung Cancers)
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Article
Prognostic Value of the Hemoglobin/Red Cell Distribution Width Ratio in Resected Lung Adenocarcinoma
Cancers 2021, 13(4), 710; https://doi.org/10.3390/cancers13040710 - 09 Feb 2021
Viewed by 673
Abstract
Background: The ratio of hemoglobin to red cell distribution width (HRR) has been described as an effective prognostic factor in several types of cancer. The aim of this study was to investigate the prognostic role of preoperative HRR in resected-lung-adenocarcinoma patients. Methods: We [...] Read more.
Background: The ratio of hemoglobin to red cell distribution width (HRR) has been described as an effective prognostic factor in several types of cancer. The aim of this study was to investigate the prognostic role of preoperative HRR in resected-lung-adenocarcinoma patients. Methods: We enrolled 342 consecutive patients. Age, sex, surgical resection, adjuvant treatments, pathological stage, preoperative hemoglobin, red cell distribution width, and their ratio were recorded for each patient. Results: Mean age was 66 years (SD: 9.0). There were 163 females (47.1%); 169 patients (49.4%) had tumors at stage I, 71 (20.8%) at stage II, and 102 (29.8%) at stage III. In total, 318 patients (93.0%) underwent lobectomy, and 24 (7.0%) pneumonectomy. Disease-free survival multivariable analysis disclosed an increased hazard ratio (HR) of relapse for preoperative HRR lower than 1.01 (HR = 2.20, 95%CI: (1.30–3.72), p = 0.004), as well as for N1 single-node (HR = 2.55, 95%CI: (1.33–4.90), p = 0.005) and multiple-level lymph node involvement compared to N0 for both N1 (HR = 9.16, 95%CI:(3.65–23.0), p < 0.001) and N2 (HR = 10.5, 95%CI:(3.44–32.2, p < 0.001). Conclusion: Pre-operative HRR is an effective prognostic factor of disease-free survival in resected-lung-adenocarcinoma patients, together with the level of pathologic node involvement. Full article
(This article belongs to the Special Issue Diagnosis and Treatment of Primary and Secondary Lung Cancers)
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Review

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Review
Recent Advances in the Diagnosis and Management of Multiple Primary Lung Cancer
Cancers 2022, 14(1), 242; https://doi.org/10.3390/cancers14010242 - 04 Jan 2022
Viewed by 234
Abstract
With the wide application of computed tomography in lung cancer screening, the incidence of multiple primary lung cancer (MPLC) has been increasingly reported. Despite the established criteria, the differentiation between MPLC and intrapulmonary metastasis remains challenging. Although histologic features are helpful in some [...] Read more.
With the wide application of computed tomography in lung cancer screening, the incidence of multiple primary lung cancer (MPLC) has been increasingly reported. Despite the established criteria, the differentiation between MPLC and intrapulmonary metastasis remains challenging. Although histologic features are helpful in some circumstances, a molecular analysis is often needed. The application of next-generation sequencing could aid in distinguishing MPLCs from intrapulmonary metastasis, decreasing ambiguity. For MPLC management, surgery with lobectomy is the main operation method. Limited resection does not appear to negatively affect survival, and it is a reasonable alternative. Stereotactic ablative radiotherapy (SABR) has become a standard of care for patients refusing surgery or for those with medically inoperable early-stage lung cancer. However, the efficacy of SABR in MPLC management could only be found in retrospective series. Other local ablation techniques are an emerging alternative for the control of residual lesions. Furthermore, systemic therapies, such as targeted therapy for oncogene-addicted patients, and immunotherapy have shown promising results in MPLC management after resection. In this paper, the recent advances in the diagnosis and management of MPLC are reviewed. Full article
(This article belongs to the Special Issue Diagnosis and Treatment of Primary and Secondary Lung Cancers)
Review
Management of Resectable Stage III-N2 Non-Small-Cell Lung Cancer (NSCLC) in the Age of Immunotherapy
Cancers 2021, 13(19), 4811; https://doi.org/10.3390/cancers13194811 - 26 Sep 2021
Viewed by 996
Abstract
Stage III non-small-cell lung cancer (NSCLC) with N2 lymph node involvement is a heterogeneous group with different potential therapeutic approaches. Patients with potentially resectable III-N2 NSCLC are those who are considered to be able to receive a multimodality treatment that includes tumour resection [...] Read more.
Stage III non-small-cell lung cancer (NSCLC) with N2 lymph node involvement is a heterogeneous group with different potential therapeutic approaches. Patients with potentially resectable III-N2 NSCLC are those who are considered to be able to receive a multimodality treatment that includes tumour resection after neoadjuvant therapy. Current treatment for these patients is based on neoadjuvant chemotherapy +/− radiotherapy followed by surgery and subsequent assessment for adjuvant chemotherapy and/or radiotherapy. In addition, some selected III-N2 patients could receive upfront surgery or pathologic N2 incidental involvement can be found a posteriori during analysis of the surgical specimen. The standard treatment for these patients is adjuvant chemotherapy and evaluation for complementary radiotherapy. Despite being a locally advanced stage, the cure rate for these patients continues to be low, with a broad improvement margin. The most immediate hope for improving survival data and curing these patients relies on integrating immunotherapy into perioperative treatment. Immunotherapy based on anti-PD1/PD-L1 immune checkpoint inhibitors is already a standard treatment in stage III unresectable and advanced NSCLC. Data from the first phase II studies in monotherapy neoadjuvant therapy and, in particular, in combination with chemotherapy, are highly promising, with impressive improved and complete pathological response rates. Despite the lack of confirmatory data from phase III trials and long-term survival data, and in spite of various unresolved questions, immunotherapy will soon be incorporated into the armamentarium for treating stage III-N2 NSCLC. In this article, we review all therapeutic approaches to stage III-N2 NSCLC, analysing both completed and ongoing studies that evaluate the addition of immunotherapy with or without chemotherapy and/or radiotherapy. Full article
(This article belongs to the Special Issue Diagnosis and Treatment of Primary and Secondary Lung Cancers)
Review
Adjuvant Treatment with Tyrosine Kinase Inhibitors in Epidermal Growth Factor Receptor Mutated Non-Small-Cell Lung Carcinoma Patients, Past, Present and Future
Cancers 2021, 13(16), 4119; https://doi.org/10.3390/cancers13164119 - 16 Aug 2021
Cited by 1 | Viewed by 702
Abstract
Lung cancer is the most common malignancy across the world. The new era in lung cancer treatments, especially this past decade, has yielded novel categories of targeted therapy for specific mutations and adjuvant therapy, both of which have led to improved survival rates. [...] Read more.
Lung cancer is the most common malignancy across the world. The new era in lung cancer treatments, especially this past decade, has yielded novel categories of targeted therapy for specific mutations and adjuvant therapy, both of which have led to improved survival rates. In the present study, we review the changes and development of treatments, with a special focus on adjuvant therapy using tyrosine kinase inhibitors (TKIs) administered to non-small-cell lung carcinoma patients who had a complete resection of the tumor harboring a mutated epidermal growth factor receptor. The clinical trials are dating from the past (chemotherapy trials), present (TKIs), and future (ongoing trials). Full article
(This article belongs to the Special Issue Diagnosis and Treatment of Primary and Secondary Lung Cancers)
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